Leukocytosis, Bone Marrow Hyperplasia and Leukemia in Chronic Magnesium Deficiency in the Rat

Mccreary, Patricia A.; Battifora, Hector; Hahneman, Betty M.; Laing, Grant H.; Hass, George M.; Singh, Katherine

doi:10.1182/blood.v29.4.683.683

Cited by 26 publications

(8 citation statements)

References 5 publications

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“…Previous observations point to the spontaneous and non-infectious induction of the inflammatory process in this experimental model (Malpuech-Brugère et al 1998). Leucocytosis was associated to cellular hyperplasia of cell lines in the bone marrow (McCreary et al 1967) while the greater spleen size in Mgdeficient rats is believed to be due to infiltration of the spleen with PMN and macrophages (Malpuech-Brugère et al 1998). Inflammatory agonists including cytokines are elevated in Mg-deficient rats (Malpuech-Brugère et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Increased phagocytosis and production of reactive oxygen species by neutrophils during magnesium deficiency in rats and inhibition by high magnesium concentration

et al. 2002

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Recent studies underline the importance of the immunoinflammatory processes in the pathology of Mg deficiency. Neutrophils possess a superoxide anion-generating NADPH oxidase and its inappropriate activation may result in tissue damage. The aim of the present study was to assess the effect of experimental Mg deficiency in the rat on polymorphonuclear leucocytes (PMN) activity and the role of increasing extracellular Mg. Weaning male Wistar rats were fed either a Mg-deficient or a control diet for 8 d. In Mg-deficient rats, the characteristic inflammatory response was accompanied by a marked increase in the number of PMN. Higher plasma interleukin 6 and NO concentrations and increased lipid peroxidation in the heart were found in Mg-deficient rats as compared with control rats. As shown by chemiluminescence studies, basal neutrophil activity from Mg-deficient rats was significantly elevated when compared with neutrophils from control rats. Moreover, the chemiluminescence of PMN from Mg-deficient rats was significantly higher than that of control rats following phorbol myristate acetate or opsonized zymosan activation. PMN from Mg-deficient rats also showed an increased activity of phagocytosis in comparison with neutrophils from control animals. Increasing extracellular Mg concentration in the incubating medium of PMN (0·8 v. 8·0 mM) decreased the chemiluminescence activity of PMN from control rats following opsonized zymosan activation. Chemiluminescence activities of PMN from Mg-deficient rats following phorbol myristate acetate or opsonized zymosan challenge were also decreased by high extracellular Mg concentration. From this work, it appears that PMN activation is an early consequence of Mg deficiency and that high extracellular Mg concentration inhibits free radicals generation.

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Section: Discussionmentioning

confidence: 99%

Increased phagocytosis and production of reactive oxygen species by neutrophils during magnesium deficiency in rats and inhibition by high magnesium concentration

et al. 2002

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“…The authors found that more than half of the bone marrow samples were hypercellular, with a greater number of granulocytic cells, and one animal developed leukemia with granulocytic infiltrate in several organs. Furthermore, cells from granulocytic infiltrate inoculated in newborn animals resulted in leukemia in half of the animals after 3 months of inoculation [ 15 ].…”

Section: The Role Of Mg 2+ In Hematopoiesismentioning

confidence: 99%

“…Studies showing the effect of disturbances in Mg 2+ homeostasis on the mechanisms of differentiation, proliferation, and maturation of hematopoietic cells in the bone marrow are rare, and there are few references in recent decades about this topic, whereby the majority of the results were obtained only in experimental models [ 15 ]. These studies demonstrated the impact of Mg 2+ deficiency on peripheral blood cells [ 4 , 5 ] or on the lymphocyte maturation process, as well as on thrombopoiesis, with a focus on the transient receptor potential cation channel subfamily M member 7 (TRPM7) channel [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

A Review of the Action of Magnesium on Several Processes Involved in the Modulation of Hematopoiesis

Lima

Fock

2020

IJMS

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Magnesium (Mg2+) is an essential mineral for the functioning and maintenance of the body. Disturbances in Mg2+ intracellular homeostasis result in cell-membrane modification, an increase in oxidative stress, alteration in the proliferation mechanism, differentiation, and apoptosis. Mg2+ deficiency often results in inflammation, with activation of inflammatory pathways and increased production of proinflammatory cytokines by immune cells. Immune cells and others that make up the blood system are from hematopoietic tissue in the bone marrow. The hematopoietic tissue is a tissue with high indices of renovation, and Mg2+ has a pivotal role in the cell replication process, as well as DNA and RNA synthesis. However, the impact of the intra- and extracellular disturbance of Mg2+ homeostasis on the hematopoietic tissue is little explored. This review deals specifically with the physiological requirements of Mg2+ on hematopoiesis, showing various studies related to the physiological requirements and the effects of deficiency or excess of this mineral on the hematopoiesis regulation, as well as on the specific process of erythropoiesis, granulopoiesis, lymphopoiesis, and thrombopoiesis. The literature selected includes studies in vitro, in animal models, and in humans, giving details about the impact that alterations of Mg2+ homeostasis can have on hematopoietic cells and hematopoietic tissue.

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“…Indeed, many studies have suggested a link between Mg 2ϩ level and cell transformation, but the findings are often inconsistent. Thus, weakly tumorigenic cultured lymphoma cells become extremely tumorigenic after growth in Mg-deficient medium (Brennan and Lichtman, 1973) and Mg deficiency is associated with a high incidence of solid lymphoma in rats (McCreary et al, 1967). Several transformed cells proliferate at an extracellular concentration of Mg 2ϩ that does not allow the growth of their normal counterparts (McKeehan and Ham, 1978;Ribeiro and Armelin, 1984;Rubin, 1982a) and a regression to the normal phenotype has been observed when transformed cells are cultured in Mg-depleted medium (Hoftiezer et al, 1985;McKeehan and McKeehan, 1980;Rubin, 1981Rubin, , 1982b.…”

mentioning

confidence: 99%

Magnesium depletion causes growth inhibition, reduced expression of cyclin D1, and increased expression of P27KIP1 in normal but not in transformed mammary epithelial cells

et al. 1999

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In this study, we have evaluated the effects of extracellular magnesium restriction on the growth and cell cycle parameters of normal (HC11) and transformed (MCF-7) breast epithelial cell lines. Cells were incubated in medium with different concentrations of Mg2+ (from 0.5 to 0 mM) and the growth rates were determined by [3H]-thymidine incorporation and cell counting. The growth of the HC11 cells was drastically inhibited by Mg2+ depletion whereas the MCF-7 cells were only slightly inhibited (about 50% and 15%, respectively, after incubation in 0.05 mM Mg for 48 h). Cell cycle analyses showed a decrease in the percentage of cells in the S phase when both cell lines were incubated at low Mg2+ concentration. However, while the percentage of cells in both the G0/G1 and G2/M phases was increased in the HC11 cells, only the percentage of cells in the G2/M phase was increased in the MCF-7 cell line. Extracellular magnesium depletion was associated with increased expression of the cyclin-dependent kinase inhibitor p27Kip1 and decreased expression of cyclin D1 in the HC11 but not in the MCF-7 cells. We also demonstrated that Mg2+ depletion does not inhibit kinase activities in the normal HC11 cells and that Mg2+-restricted HC11 cells are still responsive to the epidermal growth factor (EGF)- and insulin-mediated stimulation of cell growth. These data suggest that normal but not transformed mammary epithelial cells are inhibited by extracellular Mg2+ restriction and that this effect might be mediated by changes in the levels of expression of both cyclin D1 and p27Kip1.

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Leukocytosis, Bone Marrow Hyperplasia and Leukemia in Chronic Magnesium Deficiency in the Rat

Cited by 26 publications

References 5 publications

Increased phagocytosis and production of reactive oxygen species by neutrophils during magnesium deficiency in rats and inhibition by high magnesium concentration

Increased phagocytosis and production of reactive oxygen species by neutrophils during magnesium deficiency in rats and inhibition by high magnesium concentration

A Review of the Action of Magnesium on Several Processes Involved in the Modulation of Hematopoiesis

Magnesium depletion causes growth inhibition, reduced expression of cyclin D1, and increased expression of P27KIP1 in normal but not in transformed mammary epithelial cells

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